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Correlation of Insulin-Like Growth Factor 1 With Cognitive Functions in Mild Traumatic Brain Injury Patients 胰岛素样生长因子1与轻度外伤性脑损伤患者认知功能的相关性
Neurotrauma reports Pub Date : 2023-11-01 DOI: 10.1089/neur.2023.0085
Ju-Chi Ou, Yin-Hsun Feng, Kai-Yun Chen, Yung-Hsiao Chiang, Tsung-I Hsu, Chung-Che Wu
{"title":"Correlation of Insulin-Like Growth Factor 1 With Cognitive Functions in Mild Traumatic Brain Injury Patients","authors":"Ju-Chi Ou, Yin-Hsun Feng, Kai-Yun Chen, Yung-Hsiao Chiang, Tsung-I Hsu, Chung-Che Wu","doi":"10.1089/neur.2023.0085","DOIUrl":"https://doi.org/10.1089/neur.2023.0085","url":null,"abstract":"Mild traumatic brain injury (mTBI) is a prevalent health concern with variable recovery trajectories, necessitating reliable prognostic markers. Insulin-like growth factor 1 (IGF-1) emerges as a potential candidate because of its role in cellular growth, repair, and neuroprotection. However, limited studies investigate IGF-1 as a prognostic marker in mTBI patients. This study aimed to explore the correlation of IGF-1 with cognitive functions assessed using the Wisconsin Card Sorting Test (WCST) in mTBI patients. We analyzed data from 295 mTBI and 200 healthy control participants, assessing demographic characteristics, injury causes, and IGF-1 levels. Cognitive functions were evaluated using the WCST. Correlation analyses and regression models were used to investigate the associations between IGF-1 levels, demographic factors, and WCST scores. Significant differences were observed between mTBI and control groups in the proportion of females and average education years. Falls and traffic accidents were identified as the primary causes of mTBI. The mTBI group demonstrated worse cognitive outcomes on the WCST, except for the “Learning to Learn” index. Correlation analyses revealed significant relationships between IGF-1 levels, demographic factors, and specific WCST scores. Regression models demonstrated that IGF-1, age, and education years significantly influenced various WCST scores, suggesting their roles as potential prognostic markers for cognitive outcomes in mTBI patients. We provide valuable insights into the potential correlation of IGF-1 with cognitive functions in mTBI patients, particularly in tasks requiring cognitive flexibility and problem solving.","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"44 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135564265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) 利用新型工程旋转加速度闭合性脑损伤模型(CHIMERA)表征脑白头雪貂创伤性脑损伤模型
Neurotrauma reports Pub Date : 2023-11-01 DOI: 10.1089/neur.2023.0047
Justin L. Krieg, Anna V. Leonard, Renee J. Tuner, Frances Corrigan
{"title":"Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA)","authors":"Justin L. Krieg, Anna V. Leonard, Renee J. Tuner, Frances Corrigan","doi":"10.1089/neur.2023.0047","DOIUrl":"https://doi.org/10.1089/neur.2023.0047","url":null,"abstract":"Traumatic brain injury (TBI) results from mechanical force to the brain and leads to a series of biochemical responses that further damage neurons and supporting cells. Clinically, most TBIs result from an impact to the intact skull, making closed head TBI pre-clinical models highly relevant. However, most of these closed head TBI models use lissencephalic rodents, which may not transduce biomechanical load in the same manner as gyrencephalic humans. To address this translational gap, this study aimed to characterize acute axonal injury and microglial responses in ferrets—the smallest gyrencephalic mammal. Injury was induced in male ferrets (Mustela furo; 1.20–1.51 kg; 6–9 months old) with the novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) model. Animals were randomly allocated to either sham (n = 4), a 22J (joules) impact (n = 4), or a 27J impact (n = 4). Axonal injury was examined histologically with amyloid precursor protein (APP), neurofilament M (RMO 14.9) (RMO-14), and phosphorylated tau (AT180) and the microglial response with ionized calcium-binding adaptor molecule 1 at 24 h post-injury in gray and white matter regions. Graded axonal injury was observed with modest increases in APP and RMO-14 immunoreactivity in the 22J TBI group, mostly within the corpus callosum and fornix and more extensive diffuse axonal injury encompassing gray matter structures like the thalamus and hypothalamus in the 27J group. Accompanying microglial activation was only observed in the 27J group, most prominently within the white matter tracts in response to the larger amounts of axonal injury. The 27J, but not the 22J, group showed an increase in AT180 within the base of the sulci post-injury. This could suggest that the strain may be highest in this region, demonstrating the different responses in gyrencephalic compared to lissencephalic brains. The CHIMERA model in ferrets mimic many of the histopathological features of human closed head TBI acutely and provides a promising model to investigate the pathophysiology of TBI.","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"261 1-4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135566382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Perspectives on Data Sharing in Persons With Spinal Cord Injury 脊髓损伤患者数据共享的展望
Neurotrauma reports Pub Date : 2023-11-01 DOI: 10.1089/neur.2023.0035
Freda M. Warner, Bobo Tong, Jessie McDougall, Kathleen A. Martin Ginis, Alexander G. Rabchevsky, Jacquelyn J. Cragg, John L.K. Kramer
{"title":"Perspectives on Data Sharing in Persons With Spinal Cord Injury","authors":"Freda M. Warner, Bobo Tong, Jessie McDougall, Kathleen A. Martin Ginis, Alexander G. Rabchevsky, Jacquelyn J. Cragg, John L.K. Kramer","doi":"10.1089/neur.2023.0035","DOIUrl":"https://doi.org/10.1089/neur.2023.0035","url":null,"abstract":"Open data sharing of clinical research aims to improve transparency and support novel scientific discoveries. There are also risks, including participant identification and the potential for stigmatization. The perspectives of persons participating in research are needed to inform open data-sharing policies. The aim of the current study was to determine perspectives on data sharing in persons with spinal cord injury (SCI), including risks and benefits, and types of data people are most willing to share. A secondary aim was to examine predictors of willingness to share data. Persons with SCIs in the United States and Canada completed a survey developed and disseminated through various channels, including our community partner, the North American Spinal Cord Injury Consortium. The study collected data from 232 participants, with 52.2% from Canada and 42.2% from the United States, and the majority completed the survey in English. Most participants had previously participated in research and had been living with an SCI for ≥5 years. Overall, most participants reported that the potential benefits of data sharing outweighed the negatives, with persons with SCI seen as the most trustworthy partners for data sharing. The highest levels of concern were that information could be stolen and companies might use the information for marketing purposes. Persons with SCI were generally supportive of data sharing for research purposes. Clinical trials should consider including a statement on open data sharing in informed consents to better acknowledge the contribution of research participants in future studies.","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"90 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135564724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retrospective Observational Study of Patients With Subdural Hematoma Treated With Idarucizumab 依达鲁珠单抗治疗硬膜下血肿患者的回顾性观察研究
Neurotrauma reports Pub Date : 2023-11-01 DOI: 10.1089/neur.2023.0065
Eiichi Suehiro, Hideyuki Ishihara, Yohei Kogeichi, Tsunenori Ozawa, Koichi Haraguchi, Masaru Honda, Yumie Honda, Makoto Inaba, Ryusuke Kabeya, Naoaki Kanda, Kenta Koketsu, Nobukuni Murakami, Hidetoshi Nakamoto, Kotaro Oshio, Kuniyasu Saigusa, Takashi Shuto, Shuichi Sugiyama, Kenji Suzuyama, Tsuguaki Terashima, Mitsuharu Tsuura, Mitsutoshi Nakada, Hitoshi Kobata, Toshio Higashi, Nobuyuki Sakai, Michiyasu Suzuki
{"title":"Retrospective Observational Study of Patients With Subdural Hematoma Treated With Idarucizumab","authors":"Eiichi Suehiro, Hideyuki Ishihara, Yohei Kogeichi, Tsunenori Ozawa, Koichi Haraguchi, Masaru Honda, Yumie Honda, Makoto Inaba, Ryusuke Kabeya, Naoaki Kanda, Kenta Koketsu, Nobukuni Murakami, Hidetoshi Nakamoto, Kotaro Oshio, Kuniyasu Saigusa, Takashi Shuto, Shuichi Sugiyama, Kenji Suzuyama, Tsuguaki Terashima, Mitsuharu Tsuura, Mitsutoshi Nakada, Hitoshi Kobata, Toshio Higashi, Nobuyuki Sakai, Michiyasu Suzuki","doi":"10.1089/neur.2023.0065","DOIUrl":"https://doi.org/10.1089/neur.2023.0065","url":null,"abstract":"Use of anticoagulants is increasing with the aging of societies. The safe first-line drug is likely to be a direct oral anticoagulant (DOAC), but outcomes of treatment of traumatic brain injury (TBI) with anticoagulants are uncertain. Therefore, we examined the clinical effect of idarucizumab as reversal therapy in elderly patients with TBI who were treated with dabigatran. A retrospective multi-center observational study was performed in patients ≥65 years of age who developed acute traumatic subdural hematoma during treatment with dabigatran and underwent reversal therapy with idarucizumab. The items examined included patient background, neurological and imaging findings at arrival, course after admission, complications, and outcomes. A total of 23 patients were enrolled in the study. The patients had a mean age of 78.9 years. Cause of TBI was fall in 60.9% of the subjects. Mean Glasgow Coma Scale score at arrival was 8.7; anisocoria was present in 31.8% of cases. Exacerbation of consciousness was found in 30.4%, but only in 13.3% of subjects treated with idarucizumab before consciousness and imaging findings worsened. Dabigatran was discontinued in 81.8% of cases after hematoma development, with a mean withdrawal period of 12.1 days. The favorable outcome rate was 21.7%, and mortality was 39.1%. In multi-variate analysis, timing of idarucizumab administration was associated with a favorable outcome. There were ischemic complications in 3 cases (13.1%), and all three events occurred ≥7 days after administration of idarucizumab. These findings suggest that in cases that develop hematoma during treatment with dabigatran, it is important to administer idarucizumab early and restart dabigatran after conditions stabilize.","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"235 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135566163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antipsychotic Drugs: The Antithesis to Neurorehabilitation in Models of Pre-Clinical Traumatic Brain Injury. 抗精神病药物:临床前创伤性脑损伤模型中神经康复的拮抗剂。
IF 1.8
Neurotrauma reports Pub Date : 2023-10-31 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0082
Nicholas S Race, Eleni H Moschonas, Jeffrey P Cheng, Corina O Bondi, Anthony E Kline
{"title":"Antipsychotic Drugs: The Antithesis to Neurorehabilitation in Models of Pre-Clinical Traumatic Brain Injury.","authors":"Nicholas S Race, Eleni H Moschonas, Jeffrey P Cheng, Corina O Bondi, Anthony E Kline","doi":"10.1089/neur.2023.0082","DOIUrl":"10.1089/neur.2023.0082","url":null,"abstract":"<p><p>Sixty-nine million traumatic brain injuries (TBIs) are reported worldwide each year, and, of those, close to 3 million occur in the United States. In addition to neurobehavioral and cognitive deficits, TBI induces other maladaptive behaviors, such as agitation and aggression, which must be managed for safe, accurate assessment and effective treatment of the patient. The use of antipsychotic drugs (APDs) in TBI is supported by some expert guidelines, which suggests that they are an important part of the pharmacological armamentarium to be used in the management of agitation. Despite the advantages of APDs after TBI, there are significant disadvantages that may not be fully appreciated clinically during decision making because of the lack of a readily available updated compendium. Hence, the aim of this review is to integrate the existing findings and present the current state of APD use in pre-clinical models of TBI. The studies discussed were identified through PubMed and the University of Pittsburgh Library System search strategies and reveal that APDs, particularly those with dopamine<sub>2</sub> (D<sub>2</sub>) receptor antagonism, generally impair the recovery process in rodents of both sexes and, in some instances, attenuate the potential benefits of neurorehabilitation. We believe that the compilation of findings represented by this exhaustive review of pre-clinical TBI + APD models can serve as a convenient source for guiding informed decisions by critical care clinicians and physiatrists contemplating APD use for patients exhibiting agitation.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"724-735"},"PeriodicalIF":1.8,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association Between High-Level D-Dimer at Admission and Early Intubation in Patients With Moderate Traumatic Brain Injury. 中度颅脑损伤患者入院时高水平D-二聚体与早期插管之间的关系。
Neurotrauma reports Pub Date : 2023-10-25 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0068
Qi Zhang, Hong Min Kuang, Du Juan Qiao, Xiang Lin Zhong, Jia Jia Kang, Rui Na Ma, Min Li
{"title":"Association Between High-Level D-Dimer at Admission and Early Intubation in Patients With Moderate Traumatic Brain Injury.","authors":"Qi Zhang,&nbsp;Hong Min Kuang,&nbsp;Du Juan Qiao,&nbsp;Xiang Lin Zhong,&nbsp;Jia Jia Kang,&nbsp;Rui Na Ma,&nbsp;Min Li","doi":"10.1089/neur.2023.0068","DOIUrl":"https://doi.org/10.1089/neur.2023.0068","url":null,"abstract":"<p><p>It is unclear who can benefit from tracheal intubation in the moderate (mTBI) traumatic brain injury (TBI) population. Given that mTBI patients are conscious, intubation can cause intense stress, possibly triggering neurological deterioration. Therefore, identifying potential risk factors for intubation in mTBI patients can serve as a valuable clinical warning. We sought to investigate whether elevated D-dimer is a possible risk factor for intubation in mTBI patients. Using the STROBE statement, adult patients with isolated TBI (Glasgow Coma Scale [GCS] score 9-13) treated at a high-volume neurotrauma center between January 2015 and December 2020 were reviewed. The demographics, clinical presentation, neuroimaging, and laboratory information were collected based on the patients' electronic medical record. D-dimer values were assessed from serum when patients were admitted to the hospital. The primary study end-point was that the mTBI patient was intubated within 72 h upon admission. A total of 557 patients with mTBI were finally included in this study. Of these, 85 (15.3%) patients were intubated. Multi-variate logistic regression analysis showed that high-level D-dimer (≥17.9mg/L) was significantly associated with early tracheal intubation in mTBI patients (odds ratio, 3.10 [1.16-8.25]; <i>p</i> = 0.024) after adjusting for age, sex, GCS scores, Marshall scores, and Injury Severity Scores. Sensitivity analysis showed that high-level D-dimer had a robust correlation with intubation in the different subgroups or after propensity score matching. High-level D-dimer on admission is an independent risk factor for early tracheal intubation in isolated mTBI patients.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"715-723"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pediatric Traumatic Brain Injury in the Middle East and North Africa Region: A Systematic Review and Meta-Analysis to Assess Characteristics, Mechanisms, and Risk Factors. 中东和北非地区儿童创伤性脑损伤:评估特征、机制和危险因素的系统回顾和元分析。
IF 1.8
Neurotrauma reports Pub Date : 2023-10-17 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0007
Samar Al-Hajj, Sarah H Farran, Batoul Dekmak, Layal Hneiny, Hussein Abou Abbas, Aya Hassoun, Nadine Youness, Sarah Ghalayini, Nour Abou Khalil, Fiona Lecky, Shima Shahjouieh, Layal Ghamlouche, Zainab Nasrallah, Firas Kobeissy
{"title":"Pediatric Traumatic Brain Injury in the Middle East and North Africa Region: A Systematic Review and Meta-Analysis to Assess Characteristics, Mechanisms, and Risk Factors.","authors":"Samar Al-Hajj, Sarah H Farran, Batoul Dekmak, Layal Hneiny, Hussein Abou Abbas, Aya Hassoun, Nadine Youness, Sarah Ghalayini, Nour Abou Khalil, Fiona Lecky, Shima Shahjouieh, Layal Ghamlouche, Zainab Nasrallah, Firas Kobeissy","doi":"10.1089/neur.2023.0007","DOIUrl":"10.1089/neur.2023.0007","url":null,"abstract":"<p><p>Pediatric traumatic brain injury (pTBI) represents a major cause of child injuries in the Middle East and North Africa (MENA) region. This review aims to assess pTBIs in the MENA region and reports their clinical severity and outcomes. A search was conducted using major electronic databases, including Medline/Ovid, PubMed, EMBASE, Web of Science, and SCOPUS. Abstracts were screened independently and in duplicate to detect original research. The objective and study findings for each article were recorded, along with the mechanism of pTBI, patient age and sex, injury assessment tool(s) used, and outcome. A total of 1345 articles were retrieved, of which 152 met the criteria for full-text review, and 32 were included in this review. Males predominantly suffered from pTBIs (78%). Motor vehicle accidents, followed by child abuse, were the leading causes of pTBI. Overall, 0.39% of cases were mild, 0.58% moderate, 16.25% severe, and 82.27% unclassified. The mortality rate was 13.11%. Most studies used the computed tomography scan, Glasgow Coma Scale, Abbreviated Injury Scale, and Injury Severity Score as investigation methods. This review reports on the alarming rate of child-abuse-related pTBI and offers further understanding of pTBI-associated risk factors and insight into the development of strategies to reduce their occurrence, as well as policies to promote child well-being.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"693-714"},"PeriodicalIF":1.8,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polyurethane Culture Substrates Enable Long-Term Neuron Monoculture in a Human in vitro Model of Neurotrauma. 聚氨酯培养基能够在人类体外神经创伤模型中长期单核培养神经元。
Neurotrauma reports Pub Date : 2023-10-16 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0060
Angela Mitevska, Citlally Santacruz, Eric J Martin, Ian E Jones, Arian Ghiacy, Simon Dixon, Nima Mostafazadeh, Zhangli Peng, Evangelos Kiskinis, John D Finan
{"title":"Polyurethane Culture Substrates Enable Long-Term Neuron Monoculture in a Human <i>in vitro</i> Model of Neurotrauma.","authors":"Angela Mitevska, Citlally Santacruz, Eric J Martin, Ian E Jones, Arian Ghiacy, Simon Dixon, Nima Mostafazadeh, Zhangli Peng, Evangelos Kiskinis, John D Finan","doi":"10.1089/neur.2023.0060","DOIUrl":"10.1089/neur.2023.0060","url":null,"abstract":"<p><p>Human induced pluripotent stem cell (hiPSC)-derived cells can reproduce human-specific pathophysiology, patient-specific vulnerability, and gene-environment interactions in neurological disease. Human <i>in vitro</i> models of neurotrauma therefore have great potential to advance the field. However, this potential cannot be realized until important biomaterials challenges are addressed. <i>Status quo</i> stretch injury models of neurotrauma culture cells on sheets of polydimethylsiloxane (PDMS) that are incompatible with long-term monoculture of hiPSC-derived neurons. Here, we overcame this challenge in an established human <i>in vitro</i> neurotrauma model by replacing PDMS with a highly biocompatible form of polyurethane (PU). This substitution allowed long-term monoculture of hiPSC-derived neurons. It also changed the biomechanics of stretch injury. We quantified these changes experimentally using high-speed videography and digital image correlation. We used finite element modeling to quantify the influence of the culture substrate's thickness, stiffness, and coefficient of friction on membrane stretch and concluded that the coefficient of friction explained most of the observed biomechanical changes. Despite these changes, we demonstrated that the modified model produced a robust, dose-dependent trauma phenotype in hiPSC-derived neuron monocultures. In summary, the introduction of this PU film makes it possible to maintain hiPSC-derived neurons in monoculture for long periods in a human <i>in vitro</i> neurotrauma model. In doing so, it opens new horizons in the field of neurotrauma by enabling the unique experimental paradigms (e.g., isogenic models) associated with hiPSC-derived neurons.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"682-692"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Complement Component 5 (C5) Deficiency Improves Cognitive Outcome After Traumatic Brain Injury and Enhances Treatment Effects of Complement Inhibitors C1-Inh and CR2-Crry in a Mouse Model. 在小鼠模型中,补体组分5(C5)缺乏改善了创伤性脑损伤后的认知结果,并增强了补体抑制剂C1-Inh和CR2Crry的治疗效果。
Neurotrauma reports Pub Date : 2023-10-11 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0024
Min Chen, Stephen R Edwards, Dhiraj Maskey, Trent M Woodruff, Stephen Tomlinson, David Reutens
{"title":"Complement Component 5 (C5) Deficiency Improves Cognitive Outcome After Traumatic Brain Injury and Enhances Treatment Effects of Complement Inhibitors C1-Inh and CR2-Crry in a Mouse Model.","authors":"Min Chen, Stephen R Edwards, Dhiraj Maskey, Trent M Woodruff, Stephen Tomlinson, David Reutens","doi":"10.1089/neur.2023.0024","DOIUrl":"10.1089/neur.2023.0024","url":null,"abstract":"<p><p>A potent effector of innate immunity, the complement system contributes significantly to the pathophysiology of traumatic brain injury (TBI). This study investigated the role of the complement cascade in neurobehavioral outcomes and neuropathology after TBI. Agents acting at different levels of the complement system, including 1) C1 esterase inhibitor (C1-Inh), 2) CR2-Crry, an inhibitor of all pathways acting at C3, and 3) the selective C5aR1 antagonist, PMX205, were administered at 1 h post-TBI. Their effects were evaluated on motor function using the rotarod apparatus, cognitive function using the active place avoidance (APA) task, and brain lesion size at a chronic stage after controlled cortical impact injury in C5-sufficient (C5<sup>+/+</sup>) and C5-deficient (C5<sup>-/-</sup>) CD1 mice. In post-TBI C5<sup>+/+</sup> mice, rotarod performance was improved by CR2-Crry, APA performance was improved by CR2-Crry and PMX205, and brain lesion size was reduced by PMX205. After TBI, C5<sup>-/-</sup> mice performed better in the APA task compared with C5<sup>+/+</sup> mice. C5 deficiency enhanced the effect of C1-Inh on motor function and brain damage and the effect of CR2-Crry on brain damage after TBI. Our findings support critical roles for C3 in motor deficits, the C3/C5/C5aR1 axis in cognitive deficits, and C5aR1 signaling in brain damage after TBI. Findings suggest the combination of C5 inhibition with C1-Inh and CR2-Crry as potential therapeutic strategies in TBI.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"663-681"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plasma von Willebrand Factor Is Elevated Hyperacutely After Mild Traumatic Brain Injury. 轻度颅脑损伤后血浆血管性血友病因子升高。
Neurotrauma reports Pub Date : 2023-10-11 eCollection Date: 2023-01-01 DOI: 10.1089/neur.2023.0044
Rachel Thomas, Cillian E Lynch, Jeff Debad, Christopher Campbell, Onyinyechi Chidomere, Joseph Kilianski, Kan Ding, Christopher Madden, Danielle K Sandsmark, Ramon Diaz-Arrastia, Joshua W Gatson
{"title":"Plasma von Willebrand Factor Is Elevated Hyperacutely After Mild Traumatic Brain Injury.","authors":"Rachel Thomas, Cillian E Lynch, Jeff Debad, Christopher Campbell, Onyinyechi Chidomere, Joseph Kilianski, Kan Ding, Christopher Madden, Danielle K Sandsmark, Ramon Diaz-Arrastia, Joshua W Gatson","doi":"10.1089/neur.2023.0044","DOIUrl":"10.1089/neur.2023.0044","url":null,"abstract":"<p><p>Each year in the United States, ∼2.7 million persons seek medical attention for traumatic brain injury (TBI), of which ∼85% are characterized as being mild brain injuries. Many different cell types in the brain are affected in these heterogeneous injuries, including neurons, glia, and the brain vasculature. Efforts to identify biomarkers that reflect the injury of these different cell types have been a focus of ongoing investigation. We hypothesized that von Willebrand factor (vWF) is a sensitive biomarker for acute traumatic vascular injury and correlates with symptom severity post-TBI. To address this, blood was collected from professional boxing athletes (<i>n</i> = 17) before and within 30 min after competition. Plasma levels of vWF and neuron-specific enolase were measured using the Meso Scale Discovery, LLC. (MSD) electrochemiluminescence array-based multi-plex format (MSD, Gaithersburg, MD). Additional symptom and outcome data from boxers and patients, such as the Rivermead symptom scores (Rivermead Post Concussion Symptoms Questionnaire [RPQ-3]), were collected. We found that, subsequent to boxing bouts, there was a 1.8-fold increase in vWF levels within 30 min of injury (<i>p</i> < 0.0009). Moreover, fold-change in vWF correlates moderately (<i>r</i> = 0.51; <i>p</i> = 0.03) with the number of head blows. We also found a positive correlation (<i>r</i> = 0.69; <i>p</i> = 0.002) between fold-change in vWF and self-reported post-concussive symptoms, measured by the RPQ-3. The receiver operating curve analysis of vWF plasma levels and RPQ-3 scoring yielded a sensitivity of 94.12% and a specificity of 76.5% with an area under the curve of 83% for boxers after a fight compared to the pre-bout baseline. This study suggests that vWF is a potential blood biomarker measurable in the hyperacute period after blunt mild TBI. This biomarker may prove to be useful in diagnosing and monitoring traumatic vascular injury.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"655-662"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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